Goats and Soda: NPR

Viruses are tiny and sneaky.

So sneaky that some play a deadly game of hide and seek. The “research” part is all too familiar: they’re always looking for ways to infect humans. Their ability to hide is much less known and can have devastating consequences.

The human body is home to several effective hiding places that some of the world’s most dangerous viruses have discovered – such as the eyes and testes – that are beyond the reach of the immune system. This is where submicroscopic viral RNA can safely persist.

Human hosts often have no idea. They had gotten sick, then seemed to have beaten the virus. Their blood tested negative. They show no symptoms.

But this hidden virus is capable of coming back into action. It can emerge from hiding, either by making the original host sick or by slipping into semen or breast milk and infecting a new person.

Which viruses master this technique? A number of notorious viruses, from Zika to measles to highly deadly viruses like Nipah, Marburg and Lassa fever.

And the virus that terrified the world in 2014: Ebola.

In the decade since, the Democratic Republic of Congo has seen more than its fair share of Ebola crises – with nine outbreaks, including one ongoing – and more than its fair share of hidden viruses springing back into action.

“Almost all recent outbreaks — maybe not all but the vast majority — trace back to a previous outbreak,” says Dr. Elizabeth Higgs, who works in the Division of Clinical Research at the National Institute of Allergy and Infectious Diseases. She says once the virus’s genetics are sequenced, it’s clear that most outbreaks don’t come from an animal — like a bat — but from a human who unwittingly carried the virus after surviving a previous outbreak.

Although most survivors will never spark a new outbreak, it happens enough that Higgs says, “I think that’s the priority for research.” »

“Everyone was panicking”

Dr. Soka Moses first understood the importance of these viral hiding places ten years ago. It was mid-March 2015, when people in his West African country, Liberia, breathed a collective sigh of relief.

The country was emerging from a nightmare, remembers Moses, then medical director of an Ebola treatment center. Nearly 5,000 people died in the previous year. Some died in the streets, unable to find a hospital bed. Schools are closed, markets closed.

Finally, at the beginning of March 2015, there were no more cases of Ebola.

But the crisis was not over.

Shortly after Liberia reached zero cases, Moses remembers attending a daily meeting led by Liberia’s national outbreak response team when “boom!” A case has been identified.” As soon as the news spread, he said, “Everyone was panicking: ‘Oh, my God. Are we doing this again?'”

Part of the panic was the mystery. How could this woman have contracted Ebola when there were no active cases? The virus spreads easily when a person comes into contact with an infected person’s bodily fluids, even sweat or saliva, but it is unclear where or how this new patient might have been exposed.

Family members eventually told medical investigators the woman’s sexual partner. Five months ago, he recovered from Ebola. “[He’d] tested negative twice,” says Moses.[He was] I’m doing perfectly well, no symptoms.”

The man was terrified and initially avoided authorities. “He thought he was in really big trouble,” Moses says.

Once reassured that he had no problem, he agreed to cooperate. The challenge for scientists: to find out if the virus was hiding somewhere in his body.

They eventually determined that the Ebola virus was no longer in his blood… but was surviving in his testicles and had been transmitted through his semen.

“So it was the sexually transmitted for the first time case of Ebola virus disease,” Moses said. While he had heard of a case from 1967 in which another virus was hiding in the body, the implications were now much clearer.

This prompted Moses to act. He is today director of PREVAIL or Partnership for Research on Vaccines & Infectious Diseases in Liberia, which studies, among other things, the phenomenon of hidden viruses.

The sanctuaries of the body

Researchers have identified a number of places where viruses can hide: not only the eyes and testicles, but also the brain, the placenta and vaginal secretions as well as the mammary glands.

“We call them sanctuary sites,” says Joel Montgomerychief of the viral special pathogens branch at the U.S. Centers for Disease Control and Prevention. For the virus, they are protected refuges of the immune system.

Scientists believe this is likely because these body parts are essential for survival and vulnerable to damage if the immune system overreacts.

For example, “in the process of making eggs and sperm, we mix and match genes. So they are no longer really us,” explains Dr. John Schieffelinassociate professor at Tulane University School of Medicine. This means that the immune system may view eggs or sperm as foreign invaders and attempt to attack them. So it helps if these parts of the body are out of reach of the immune system.

The brain benefits from a particular level of protection in the blood-brain barrier which limits the entry of immune cells. As for the eye? “An ophthalmologist might scold me for this, but to me it’s really an extension of the brain. There’s a big nerve that goes from your eye straight into your brain,” says Schieffelin.

Lots of mysteries

There is still much that scientists do not know about the behavior of viruses in these sanctuary sites.

For example, exactly how long can a virus stay there? In many cases where individuals have been tested, it appears to be a matter of months. In some cases it takes years. There have even been semen samples that tested negative for the virus at one point and then came back positive later. Scientists aren’t sure what drove this reversal. And researchers haven’t followed enough people who have been infected with one of these infections for long enough to know the outer limit.

Another big unknown: what is the virus doing on the sanctuary site? It appears to be almost dormant, barely reproducing. “But we don’t know why someone relapses. We don’t know if it’s a drop in their immune system or if there’s some other factor,” Montgomery says.

Fear and stigma

Montgomery says the goal is to identify medications for survivors that can reach sanctuary sites and eliminate any hidden viruses. For this, he says, the size of the molecule contained in the drug is essential.

“We really need to explore the use of small-molecule drugs,” he says, suggesting that the smaller the drug molecule, the more likely it is to penetrate the protective barrier around a sanctuary site.

Moses’ team studied exactly that with the drug remdesivir – and the results were promising. Survivors who received the drug cleared the virus from their sperm more quickly than survivors who received the placebo.

While many researchers focus on biology, the psychological part of the equation is never far from their minds. Ebola survivors can face intense fear and stigma.

When Dr. Dehkontee Dennis – who works at PREVAIL in Liberia – signed up for the study, she says she noticed “there was one thing that all of these men expressed: They have this fear. They do not want to transmit the virus to their family. They want to have children. They want to stop using condoms [to prevent transmission]”.

The flip side is that many community members – who may have lost partners and other family members to Ebola – fear that survivors still pose a threat, even if they don’t know about shelter sites. “Community members didn’t even want them to come back to their communities,” Moses says.

This level of stigma makes it difficult to talk about the risk that the virus could hide in a survivor and then resurface. Survivors and their communities need to know that there is a chance of this happening, scientists say – but only in a small percentage of cases.

Comfort can also come from survivor programs that test sperm and vaccination campaigns to protect the community. But scientists say the solution will lie in finding drugs that can detect these hidden and potentially deadly viruses.

“It’s great that we have vaccines,” says Joel Montgomery of the CDC. “It’s great that we have therapeutic treatments. It’s great that we’re saving lives. But now we have to find a way to make sure the virus is completely eliminated from them.”